Interleukin-1 Polymorphism and Expression in Hepatitis B Virus-Mediated Disease Outcome in India

Abstract

The present study evaluated any possible association among Interleukin-1-beta (IL-1B)-511 and IL-1 receptor antagonist (IL-1RN) variable number tandem-repeat (VNTR) genotypes, haplotypes, and IL-1B expression with risk for hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) development in India. For this, 406 subjects (153 controls, 67 inactive HBV-carriers, 65 patients with chronic-active HBV, 62 HBV-cirrhotics, and 59 subjects with HBV-HCC) were enrolled in the study. Polymerase chain reaction (PCR)–restriction fragment length polymorphism, reverse transcriptase–PCR, and enzyme-linked immunosorbent assay methods were used for assessing polymorphism, mRNA, and protein levels, respectively, of IL-1. The study revealed no significant association of IL-1B(−511) CT and TT genotypes, while a significant positive association of the IL-1RN (VNTR) 1/2 genotype with HCC development, among controls and carriers. Besides, 2/2 genotypes acted as a potential risk factor for hepatitis and subsequent cirrhosis development, among the same groups. Furthermore, the IL-1 haplotypes 2 and 3 were found to be significant protective factors for hepatitis and subsequent HCC development, among controls. However, haplotype 4 shared a significant negative association with hepatitis only. Moreover, proinflammatory IL-1B levels significantly and steadily elevated with the disease progression to HCC, as compared to controls. These preliminary findings indicate a key role of IL-1 in the HBV-mediated disease chronicity, in the Indian population.